Category Archives: PSP

This article out of Mount Sinai School of Medicine reviews studies in lab animals of GSPE (grape seed-derived polyphenolic extracts) in the treatment of tauopathies such as PSP, CBD, and AD. My impression is that most of the studies reviewed were done by researchers at Mount Sinai School of Medicine!

The researchers note: “Recent studies from our laboratory reveal that grape seed-derived polyphenolic extracts (GSPE) potently prevent tau fibrillization into neurotoxic aggregates and therapeutically promote the dissociation of preformed tau aggregates.”

The abstract indicates that this research team “initiated a series of studies exploring the role of GSPE (Meganatural-Az® GSPE) as a potential novel botanical drug for the treatment of certain forms of tauopathies including PSP…”

You can find more information on this product from this website promoting it:
http://www.meganaturalbp.com/polyphenolics/
They say they have FDA GRAS status (generally recognized as safe). This simply means the FDA views the chemical as safe, not that the FDA has approved of it as a drug that can be used for certain medical conditions. The disclosure section of the article indicates: “Drs. Pasinetti, Wang and Ho are named inventors of a pending patent application filed by Mount Sinai School of Medicine (MSSM) for grape seed polyphenolic extract.”

I assumed GSPE was the same thing as resveratrol. According to the article, “no detectable resveratrol is found in Meganatural-Az® GSPE.”

I couldn’t glean much about the “series of studies” in PSP. I don’t know if these are all biochemistry studies done in petri dishes or studies using lab animals. Some human studies must be going on as well because the article says: “Tolerability and dose escalation studies in PSP subjects are presently underway in our Institution, and will provide fundamental information for the characterization of appropriate doses of Meganatural-Az® GSPE in the treatment of PSP.”

The authors state: “In conclusion, our studies tentatively support the hypothesis, for the first time, that certain forms of bioavailable polyphenolic compounds in Meganatural-Az® GSPE may promote tau anti-oligomerization activities in the brain, ultimately delaying clinical PSP onset, and possibly therapeutically attenuating the clinical progression of PSP and other tauopathies.”

If anyone looks into this further, please share!

Robin

Journal of Neurochemistry. 2010 Jun 20. [Epub ahead of print]

Development of a grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies.

Pasinetti GM, Ksiezak-Reding H, Santa-Maria I, Wang J, Ho L.
Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics, Brain Institute, Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer’s Disease, Department of Neurology, Mount Sinai School of Medicine, New York, NY.

Abstract
A diverse group of neurodegenerative diseases – including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer’s disease (AD) among others, collectively referred to as tauopathies – are characterized by progressive, age-dependent intracellular formations of misfolded protein aggregates that play key roles in the initiation and progression of neuropathogenesis.

Recent studies from our laboratory reveal that grape seed-derived polyphenolic extracts (GSPE) potently prevent tau fibrillization into neurotoxic aggregates and therapeutically promote the dissociation of preformed tau aggregates (Ho et al., 2009).

Based on our extensive bioavailability, bioactivity and functional pre-clinical studies, combined with the safety of GSPE in laboratory animals and in humans, we initiated a series of studies exploring the role of GSPE (Meganatural-Az((R)) GSPE) as a potential novel botanical drug for the treatment of certain forms of tauopathies including PSP, a neurodegenerative disorder involving the accumulation and deposition of misfolded tau proteins in the brain characterized, in part, by abnormal intracellular tau inclusions in specific anatomical areas involving astrocytes, oligodendrocytes and neurons (Takahashi et al., 2002).

In this mini-review article, we discuss the biochemical characterization of GSPE in our laboratory and its potential preventative and therapeutic role in model systems of abnormal tau processing pertinent to PSP and related tauopathies.

PubMed ID#: 20569300 (see pubmed.gov for this abstract)

In this Japanese PET study, acetylcholinesterase activity in the brain was measured in seven CBS patients, 12 PSP patients, and 8 FTD (frontotemporal dementia) patients.

Acetylcholine is a neurotransmitter that helps with cognition. By measuring “acetylcholinesterase activity, we can assess the integrity of the…cholinergic system.”

“Cerebral cortical acetylcholinesterase activity was moderately reduced in corticobasal syndrome and mildly reduced in progressive supranuclear palsy, while thalamic acetylcholinesterase activity was remarkably reduced only in progressive supranuclear palsy.”

The FTD group showed no decline in acetylcholinesterase activity. The authors make the point that acetylcholinesterase inhibitors (AChEIs include Aricept, Exelon, and Razadyne) are of no value in FTD.

The authors “found a correlation between MMSE scores and cortical acetylcholinesterase activity in the corticobasal syndrome group, suggesting that cognitive decline might be caused by cholinergic dysfunction in corticobasal syndrome.” From those in our local support group and on the CBD-related Yahoo!Group, it seems that AChEIs are of limited value in CBS.

Anecdotal evidence also indicates that AChEIs are of limited value in PSP. Further, the authors note: “In spite of the mounting evidence of cholinergic impairment in the brain of patients with progressive supranuclear palsy, a number of drug trial studies have failed to show beneficial effects of cholinergic stimulant therapy. … Other forms of acetylcholine modulating agent might be helpful for improving clinical symptoms in patients with progressive supranuclear palsy.” I’m not sure what “other forms” includes.

The authors compare the cholinergic deficits in CBS and PSP to those with Alzheimer’s Disease and other disorders. “We have studied brain acetylcholinesterase activity in other neurodegenerative diseases by PET and found that mean reduction of cortical acetylcholinesterase activity, compared with normal controls, was 13% in mild to moderate late-onset Alzheimer’s disease, 23% in mild to moderate early-onset Alzheimer’s disease, 12% in Parkinson’s disease without dementia, 27% in Parkinson’s disease with dementia and dementia with Lewy bodies, 21 and 36% in two patients with N279K FTDP-17 and 6% in a cerebellar variant of multiple system atrophy. Compared with the reduction of cortical acetylcholinesterase activities in these disorders, the reduction of cortical acetylcholinesterase was moderate [17.5%] in corticobasal syndrome and mild [9.4%] in progressive supranuclear palsy.”

I’ve copied the abstract below.

Robin

Brain. 2010 Jun 17. [Epub ahead of print]

Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia.

Hirano S, Shinotoh H, Shimada H, Aotsuka A, Tanaka N, Ota T, Sato K, Ito H, Kuwabara S, Fukushi K, Irie T, Suhara T.
Molecular Neuroimaging Group, Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.

Abstract
Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders.

We measured brain acetylcholinesterase activity by [(11)C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6 +/- 5.9 years), 12 with progressive supranuclear palsy (68.5 +/- 4.1 years), eight with frontotemporal dementia (59.8 +/- 6.9 years) and 16 healthy controls (61.2 +/- 8.5 years).

Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k(3) value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k(3) images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k(3) images.

The corticobasal syndrome group showed decreased acetylcholinesterase activity (k(3) values) in the paracentral region, frontal, parietal and occipital cortices (P < 0.05, cluster corrected).

The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P < 0.05, cluster corrected).

The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity.

Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P < 0.001), 9.4% in progressive supranuclear palsy (P < 0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P < 0.03) and increased by 3.3% in frontotemporal dementia (non-significant).

Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.

PubMed ID#: 20558417 (see pubmed.gov for this abstract only)